Song Lab

Department of Neurology

Office 2012, 114 16th Street
114 16th Street
Charlestown, MA  02129

Email: Yuyu Song (PI): ysong13@mgh.harvard.edu

    Overview

    We are a young, energetic, and innovative group in the Department of Neurology at Mass General Hospital and Harvard Medical School. We are associated with MassGeneral Institute for Neurodegenerative Disease (MIND) and are affiliated with the Massachusetts Alzheimer's Disease Research Center (MADRC). We also have active summer research programs at the Marine Biological Laboratory at Woods Hole and exciting collaborations with various laboratories at Harvard and beyond.  

    Group Members

    • Yuyu Song, M.D., Ph.D., PI, Assistant Professor of Neurology, Massachusetts General Hospital and Harvard Medical School
    • Tanner Boyd, Research Associate, Massachusetts General Hospital
    • Sonia Okekenwa, Research Associate, Massachusetts General Hospital
    • Ellia Chiang, 2023 Summer Intern, Williams College
    • Ruoran Cheng, 2022 Summer Intern, Durham University, UK

    Research Projects

    • Neuronal Cytoskeletal Dynamics and Stability
    • Intracellular Trafficking, Motor Proteins, and Neuronal Signaling in Health and Disease
    • Protein Misfolding and Chaperones in Tauopathies and ALS
    • Synaptic Actions of Misfolded Proteins and Calcium Signaling
    • Molecular Mechanisms and Potential Therapeutic Approaches for Neurodegenerative Diseases (e.g., ALS, AD, HD, etc.)
    • Development of multi-omics studies, multiplexed and high-content imaging techniques, and super-resolution imaging methods in various animal and human model systems.

    Research Positions

    • Postdoctoral Fellows
    • Research Technicians
    • Graduate Students
    • Undergraduate Students
    • Summer Interns

    News and Events

    Publications

    Research Investigations:

    Bosco, D.A., Morfini, G., Karabacak, N.M., Song, Y., Gros-Louis, F., Pasinelli, P., Goolsby, H., Fontaine, B.A., Lemay, N., McKenna-Yasek, D., Frosch, M.P., Agar, J.N., Julien, J.P., Brady, S.T., and Brown, R.H., Jr., Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS. Nat Neurosci, 2010. 13(11): p. 1396-403.

    Kanaan, N.M., Morfini, G.A., LaPointe, N.E., Pigino, G.F., Patterson, K.R., Song, Y., Andreadis, A., Fu, Y., Brady, S.T., and Binder, L.I., Pathogenic forms of tau inhibit kinesin-dependent axonal transport through a mechanism involving activation of axonal phosphotransferases. J Neurosci, 2011. 31(27): p. 9858-68.

    Cederquist, G.Y., Luchniak, A., Tischfield, M.A.*, Peeva, M.*, Song, Y.*, Menezes, M.P., Chan, W.M., Andrews, C., Chew, S., Jamieson, R.V., Gomes, L., Flaherty, M., Grant, P.E., Gupta, M.L., Jr., and Engle, E.C., An inherited TUBB2B mutation alters a kinesin-binding site and causes polymicrogyria, CFEOM and axon dysinnervation. Hum Mol Genet, 2012. 21(26): p. 5484-99. (* Co-2nd author)

    Kanaan, N.M., Morfini, G., Pigino, G., LaPointe, N.E., Andreadis, A., Song, Y., Leitman, E., Binder, L.I., and Brady, S.T., Phosphorylation in the amino terminus of tau prevents inhibition of anterograde axonal transport. Neurobiol Aging, 2012. 33(4): p. 826 e15-30.

    Cantuti Castelvetri, L., Givogri, M.I., Hebert, A., Smith, B., Song, Y., Kaminska, A., Lopez-Rosas, A., Morfini, G., Pigino, G., Sands, M., Brady, S.T., and Bongarzone, E.R., The sphingolipid psychosine inhibits fast axonal transport in Krabbe disease by activation of GSK3beta and deregulation of molecular motors. J Neurosci, 2013. 33(24): p. 10048-56.

    Morfini, G.A., Bosco, D.A., Brown, H., Gatto, R., Kaminska, A., Song, Y., Molla, L., Baker, L., Marangoni, M.N., Berth, S., Tavassoli, E., Bagnato, C., Tiwari, A., Hayward, L.J., Pigino, G.F., Watterson, D.M., Huang, C.F., Banker, G., Brown, R.H., Jr., and Brady, S.T., Inhibition of fast axonal transport by pathogenic SOD1 involves activation of p38 MAP kinase. PLoS One, 2013. 8(6): p. e65235.

    Song, Y. and Brady, S.T., Analysis of microtubules in isolated axoplasm from the squid giant axon. Methods Cell Biol, 2013. 115: p. 125-37.

    Song, Y., Kirkpatrick, L.L., Schilling, A.B., Helseth, D.L., Chabot, N., Keillor, J.W., Johnson, G.V., and Brady, S.T., Transglutaminase and polyamination of tubulin: posttranslational modification for stabilizing axonal microtubules. Neuron, 2013. 78(1): p. 109-23.

    Song, Y., Nagy, M., Ni, W., Tyagi, N.K., Fenton, W.A., Lopez-Giraldez, F., Overton, J.D., Horwich, A.L., and Brady, S.T., Molecular chaperone Hsp110 rescues a vesicle transport defect produced by an ALS-associated mutant SOD1 protein in squid axoplasm. Proc Natl Acad Sci U S A, 2013. 110(14): p. 5428-33.

    Song, Y. and Brady, S.T., Post-translational modifications of tubulin: pathways to functional diversity of microtubules. Trends Cell Biol, 2015. 25(3): p. 125-36.

    Barry, J.F., Turner, M.J., Schloss, J.M., Glenn, D.R., Song, Y., Lukin, M.D., Park, H., and Walsworth, R.L., Optical magnetic detection of single-neuron action potentials using quantum defects in diamond. Proc Natl Acad Sci U S A, 2016. 113(49): p. 14133-14138.

    Berth, S.H., Mesnard-Hoaglin, N., Wang, B., Kim, H., Song, Y., Sapar, M., Morfini, G., and Brady, S.T., HIV Glycoprotein Gp120 Impairs Fast Axonal Transport by Activating Tak1 Signaling Pathways. ASN Neuro, 2016. 8(6).

    Kang, M., Baker, L., Song, Y., Brady, S.T., and Morfini, G., Biochemical analysis of axon-specific phosphorylation events using isolated squid axoplasms. Methods Cell Biol, 2016. 131: p. 199-216.

    Song, Y., Kang, M., Morfini, G., and Brady, S.T., Fast axonal transport in isolated axoplasm from the squid giant axon. Methods Cell Biol, 2016. 131: p. 331-48.

    Leo, L., Weissmann, C., Burns, M., Kang, M., Song, Y., Qiang, L., Brady, S.T., Baas, P.W., and Morfini, G., Mutant spastin proteins promote deficits in axonal transport through an isoform-specific mechanism involving casein kinase 2 activation. Hum Mol Genet, 2017. 26(12): p. 2321-2334.

    Sama, R.R., Fallini, C., Gatto, R., McKeon, J.E., Song, Y., Rotunno, M.S., Penaranda, S., Abdurakhmanov, I., Landers, J.E., Morfini, G., Brady, S.T., and Bosco, D.A., ALS-linked FUS exerts a gain of toxic function involving aberrant p38 MAPK activation. Sci Rep, 2017. 7(1): p. 115.

    Zamponi, E., Buratti, F., Cataldi, G., Caicedo, H.H., Song, Y., Jungbauer, L.M., LaDu, M.J., Bisbal, M., Lorenzo, A., Ma, J., Helguera, P.R., Morfini, G.A., Brady, S.T., and Pigino, G.F., Prion protein inhibits fast axonal transport through a mechanism involving casein kinase 2. PLoS One, 2017. 12(12): p. e0188340.

    Pineda, J.J., Miller, M.A., Song, Y., Kuhn, H., Mikula, H., Tallapragada, N., Weissleder, R., and Mitchison, T.J., Site occupancy calibration of taxane pharmacology in live cells and tissues. Proc Natl Acad Sci U S A, 2018. 115(48): p. E11406-E11414.

    Shimada, K., Reznik, E., Stokes, M.E., Krishnamoorthy, L., Bos, P.H., Song, Y., Quartararo, C.E., Pagano, N.C., Carpizo, D.R., deCarvalho, A.C., Lo, D.C., and Stockwell, B.R., Copper-Binding Small Molecule Induces Oxidative Stress and Cell-Cycle Arrest in Glioblastoma-Patient-Derived Cells. Cell Chem Biol, 2018. 25(5): p. 585-594 e7.

    Song, Y. *#, Subramanian, K. *, Berberich, M.J. *, Rodriguez, S., Latorre, I.J., Luria, C.M., Everley, R., Albers, M.W., Mitchison, T.J., and Sorger, P.K. #, A dynamic view of the proteomic landscape during differentiation of ReNcell VM cells, an immortalized human neural progenitor line. Nature/Sci Data, 2019. 6: p. 190016. (*Co-1st author, #Co-corresponding author).

    Song, Y., Synaptic Actions of Amyotrophic-Lateral-Sclerosis-Associated G85R-SOD1 in the Squid Giant Synapse. eNeuro, 2020. (Sole author)

    Other scholarship

    Morfini, G.A., Burns, M., Binder, L.I., Kanaan, N.M., LaPointe, N., Bosco, D.A., Brown, R.H., Jr., Brown, H., Tiwari, A., Hayward, L., Edgar, J., Nave, K.A., Garberrn, J., Atagi, Y., Song, Y.,

    Pigino, G., and Brady, S.T., Axonal transport defects in neurodegenerative diseases. J Neurosci, 2009. 29(41): p. 12776-86. Pigino, G.,

    Song, Y., Kirkpatrick, L.L., and Brady, S.T., The Cytoskeleton of Neurons and Glia, in Basic Neurochemistry: Principles of Molecular, Cellular and Medical Neurobiology, S.T. Brady, G. Siegel, R.W. Albers, and D. Price, Editors. 2012, Elsevier: Boston. p. 101-118.

    Song, Y. and Brady, S.T., Tubulin Mutations and Neurological Diseases, in Basic Neurochemistry: Principles of Molecular, Cellular and Medical Neurobiology, S.T. Brady, G. Siegel, R.W. Albers, and D. Price, Editors. 2012, Elsevier: Boston. p. 115-116.

    Song, Y. and Brady, S.T., Stabilization of neuronal connections and the axonal cytoskeleton. Bioarchitecture, 2014. 4(1): p. 22-4.

    Song, Y. and Berberich, M., ReNcell differentiation: Total proteomics during differentiation under basal conditions. NIH HMS LINCS 2018.

    Song, Y. and Berberich, M., ReNcell differentiation: Total proteomics during differentiation with small molecule perturbagens. NIH HMS LINCS, 2018.

    Song, Y. and Berberich, M., ReNcell differentiation: Phosphoproteomics during differentiation under basal conditions. NIH HMS LINCS, 2018.

    Song, Y. Synapse https://doi-org.ezp-prod1.hul.harvard.edu/10.7303/syn11667815 (2018)

    Song, Y. Synaptic actions of an ALS-associated protein in the giant squid synapse. Scientific Research Summary, Neuronline, SFN Journals, 2020.

    Georgescauld, F., Song, Y., Dautant, A., Structure, Folding and Stability of Nucleoside Diphosphate Kinases, International Journal of Molecular Sciences, 2020 Sep 16;21(18):6779. doi: 10.3390/ijms21186779. PMID: 32947863; PMCID: PMC7554756